Excited to share that our Biobank at Sapien Biosciences and the patient cancer-derived cell models developed by Saarum Sciences Private Limited were covered by India Today as part of their COVER STORYdevoted to innovation in India in the fight against Cancer (26th June issue). Kudos to Damayanti Datta for putting together a detailed summary for lay people to better understand the concepts and buzz words doing the rounds, and to India Today for in-depth coverage of science and healthcare. Big Thanks to Aroon Puri for citing us in the EDITOR’S NOTE as well.

This is a retrospective study with data collected from breast cancer cases from five major Apollo Hospitals across India, as part of a biobanking process. One aspect of our study focused specifically on data from triple-negative breast cancer (TNBC) cases. The aim of this study was to analyze epidemiology, treatment options, and survival of the patients with TNBC. Our goal was to draw conclusions on the preponderance of the disease and also to understand the outcomes using the existing therapy options. MATERIALS AND METHODS: Data were collected after due ethical clearances and were coded with regard to patient identifiers to protect patient privacy. Data were not only from the various departments of the respective hospitals and the treating physicians but also from the follow-up made by hospital staff and social workers. RESULTS: About 20% of all cases of breast cancer comprised TNBC. Although the disease is generally thought to be an early onset disease, there was no major difference in the median age of diagnosis of TNBC compared to other breast cancer cases. More than 85% of the TNBC cases were of early stage disease with <4% of the cases of metastatic cancer. Data on follow-up were somewhat sporadic as a good number of cases were lost to follow-up, but from the available data, recurrence rate was about 11%. Death, when it occurred, was mostly in the early periods of treatment with 35% of the events occurring before 3 years. The overall survival rates beyond 3 years were more than 86%. CONCLUSIONS: Data and sample collection are an ongoing process, so we expect this data set to be enriched with more cases and longer duration of follow-up in a year. Preliminary analysis sheds light on the potential of such a collection both for understanding the epidemiology of the disease and also for conducting future studies with an eye toward improving treatment outcomes.

Sapien is collaborating with Dr. Joglekar’s group at Boston University to mine Sapien’s cardiac patients database. Our goal is to jointly analyse patterns of usage of different stents, blood thinning medicines, co-medications, myPlatelet assay , follow-up visits and monitoring with an eye towards optimizing implementation of personalized treatment to improve patient outcomes.

Over the last three years, Sapien Biosciences, working with leading cardiologists Dr. PC Rath and Dr. PK Sahoo at Apollo Hospitals, and Dr. A Yerramilli at SV College of Pharmacy, have collated a detailed dataset of approximately 800 coronary artery disease patients who underwent a PCI-stent procedure. These patients were prescribed various anti-platelet therapies (APTs), branded or generic versions of clopidogrel, prasugrel, ticagrelor, as part of their maintenance regimen for a year or more to prevent restenosis. About half of these patients also took Sapien’s myPlatelet test (myPlatelet brochure), a combination genetic and functional test, to check the effectiveness of the APTs they were prescribed. These ~800 patients have been followed up for a year to determine the success of their treatment regimens and document any significant adverse events. This rich dataset is being used to perform cost-benefit analysis of different treatment paradigms in the Indian healthcare delivery context.

Appropriate ethical IEC/IRB clearances have been taken by each party to share de-identified data. These analyses are expected to be published and pave the way for additional studies including assessing the impact of patient engagement in improving outcomes.

myPlatelet test is a combination of genetic profiling for the presence of common variants of CYP2C19 gene that affect the bioavailability of clopidogrel , and a platelet function test for evaluating platelet reactivity. It is highly specific and sensitive compared to the commonly used Light Transmission Aggregometry (LTA), and correlates well with the plasma levels of anti-platelet medication. It is able to detect high risk of thrombosis or blood clotting as well as excessive bleeding. The value of this assay in preventing post-procedural major adverse cardiac events or MACE in patients who underwent PCI has been demonstrated in several studies world-wide as summarized in this publication.

Sapien is India’s largest commercial biobank, repurposing human medical waste to discover and validate clinically useful prognostics, diagnostics & theranostics to optimize the diagnosis and treatment of individual patients. It has curated over 55000 patients’ samples and associated data spanning most diseases plus access to more than 1.5 million healthy and diseased individuals. It follows Indian medical council (ICMR) guidelines and works closely with Institutional Ethics Committees to ensure ethical and regulatory compliance.

Dr. Nitin Joglekar is Associate Professor of Operations and Technology Management, and Dean’s Research Fellow, at Boston University Questrom School of Business. His interests span development of products, supply chains and customer engagement at established and entrepreneurial organizations.

Conclusions: Breast cancer management strategies vary in Indian and US populations. Indian patients are younger with tumor sizes amenable to BCT followed by loco-regional radiotherapy. Despite this, only a minority of patients opted for BCT. In the hormone-positive population, majority of patients received chemotherapy in addition to hormone therapy due to high incidence of node positivity, tumor size>2 cm and unaffordability of genomic assays. In the Her2+ population, trastuzumab use was limited, reportedly due to cost. Overall, management is adapted to limited resources and follow-up is inconsistent. It may be beneficial to set up Indian national breast cancer guidelines to promote multidisciplinary management, describe the molecular features of disease in this population, and evaluate the cost-effectiveness of expensive diagnostic and therapeutic interventions. This will encourage rational policies and help to create a comprehensive cancer treatment network.

Glycoprotein NMB (gpNMB) is a transmembrane protein and tumor-associated antigen that is expressed at higher levels in certain malignancies than in normal tissues. Glembatumumab vedotin (CDX-011) is an antibody-drug conjugate consisting of a fully human IgG2 monoclonal antibody against gpNMB linked to the microtubule inhibitor monomethyl auristatin E (MMAE). By targeting and binding to cells overexpressing gpNMB, the antibody is internalized, allowing for intracellular release of the cytotoxic MMAE.

ORR was similar overall for patients receiving CDX-011 or IC (6% and 7%, respectively) and for those with gpNMB-expressing tumors (12% for both). ORR was higher with CDX-011 versus IC in patients with ≥25% of tumor cells expressing gpNMB (30% vs. 9%) as well as in TNBC patients (18% vs. 0%) and TNBC patients with overexpression of gpNMB (40% vs. 0%). Dose reduction occurred in 25% of patients in both treatment arms. The most common CDX-011 toxicities were rash, fatigue, nausea, neutropenia, and neuropathy.

Comment
The attraction of targeted therapy with an antibody delivery system is that it directs the cytotoxic agent preferentially to the malignant cell population, potentially enhancing efficacy and minimizing systemic toxicity. The use of ado-trastuzumab emtansine for HER2-positive breast cancer demonstrates the success of this approach (NEJM JW Oncol Hematol Sep 2014 and J Clin Oncol 2014; 32:2750). The signal that CDX-011 is active in TNBC is exciting, but the observations from this study are based on very small numbers of patients. A larger, pivotal phase II trial (METRIC) is under way to more fully investigate this compound in TNBC.